PROJECT SUMMARY/ABSTRACT Living donor kidney transplantation (LDKT) is promoted to redress the shortage of kidneys for transplantation. However, studies show that living donors (LDs) have a greater risk of kidney failure than healthy non-LDs post-donation.4-6 Moreover, African American (AA) LDs have an even greater risk of kidney failure post-donation than European American (EA) LDs.4,5 These findings have generated heightened concerns in the transplant community over protecting LDs' safety and improving LDs' informed consent.7-14 Genetics may help explain this disparity. Genetics research found that Apolipoprotein L1 (APOL1) gene variants (1-2 alleles) are significantly associated with kidney failure predominantly in AAs.15-19 Kidney transplants from deceased donors with APOL1 variants had significantly shorter survival than kidneys from donors without variants.20 APOL1 variants may explain why AA LDs have a greater risk of kidney failure post- donation than do EA LDs.5,6,20 Thus, testing AA potential LDs for APOL1 variants could better risk stratify them. Little is known about the transplant community's attitudes about and practices of integrating APOL1 genetic testing into the routine clinical evaluation of AA LDs. No guidelines exist for genetic testing in transplantation. While proponents believe that the evidence is strong enough to warrant APOL1 testing,21,22 critics counter that testing is premature.23 Yet some transplant centers are using APOL1 testing routinely,22 or on a case-by-case basis. Transplant centers' practices are ethically charged: (not) using APOL1 testing could harm AA LDs. LDs unknowingly with the variants might make less informed decisions and unnecessarily undergo donation, which would violate the ethical principle of non-maleficence, as LDs gain no direct medical benefit from donation.25-27 Conversely, by learning they had APOL1 variants, LDs may choose to not donate to protect themselves or prevent the recipient from getting a kidney with potentially lower graft survival. Testing may also affect AAs' cultural identity, which in turn could shape attitudes about LDs' willingness to use APOL1 testing. The objective of this study is to assess the ethical and sociocultural implications of physicians' use of APOL1 testing for AA LDs, and to develop culturally sensitive educational materials for genetic counseling about APOL1 testing. We will assess the transplant community's normative expectations, attitudes, and current practices about testing AA potential LDs for APOL1 variants through a national survey. We will also assess AA LDs' information preferences, attitudes about, and willingness to be tested for APOL1 variants through semi-structured interviews. The results will inform the development of culturally sensitive education materials for genetic counseling about APOL1 testing, which will be refined by focus groups with AA LDs. The proposed study is timely because APOL1 testing could increase AA potential LDs' safety and reduce disparities in AA LD outcomes. This study facilitates NHGRI's initiative to better understand the implementation of emerging clinical genomics into clinical practice,32 consistent with the NIH's precision medicine's initiative.33